2.1 Testicular Cancer
Testicular cancer represents only about 1% of all cancers in males, but it is the most common cancer in young men between the ages of 15 and 35 years old. In the year 2000, an estimated 7,600 cases of testicular cancer was diagnosed in the United States, and approximately 400 deaths. Caucasians are more likely to get testicular cancer than Hispanics, and much more likely to get it than Blacks or Asians. The incidence of testicular cancer is highest in Denmark, and lowest in the far east. Disturbingly, the incidence of testicular cancer around the world has almost doubled in the past 30 to 40 years.
Typically, there are no early symptoms. Most testicular cancers are found by men themselves, either as a painless lump, a hardening or a change (increase or decrease) in size of the testicle, a feeling of heaviness or a sudden collection of fluid in the scrotum, a dull ache in the lower abdomen or in the groin, or pain or discomfort in the scrotum or testicle. Generalized symptoms are usually indicative of metastasis, such as pulmonary metastasis, causing dyspnea or hemoptysis, abdominal mass, or urethral obstruction by lymph node involvement. Sometimes other symptoms may be present, such as backache, stomach-ache, breathlessness, a persistent dry cough, and tender nipples. Nevertheless, early diagnosis of testicular cancer is especially important because testicular cancer is almost always curable if it is found early. If the cancer is not treated, cancer cells from the original site may break away and spread to nearby lymph nodes but, rarely, to other organs.
The only sure way to know whether testicular cancer is present is by performing a biopsy. To date, the cause of testicular cancer is unknown. Children born with an undescended testicle or cryptorchidism have an increased risk (3 to 14 times) of getting testicular cancer regardless of whether surgery is done to correct the problem. (Farer et al., 1985, J. Urol. 134:1071–1076). Research has also shown that testicular cancer is sometimes linked to certain other rare conditions in which the testicles do not develop normally. Studies indicate that some men whose mothers took a hormone called DES (diethylstilbestrol) during pregnancy to prevent miscarriage may develop testicular abnormalities. Some patients with testicular cancer have a history of injury to the scrotum. There is no evidence that an injury or a sporting strain increases the risk of developing testicular cancer. Other risk factors include previous testicular cancer in one testicle, infection with the human immunodeficiency virus (HIV), particularly if acquired immune deficiency syndrome (AIDS) has developed, and the sex chromosome disorder Klinefelter's syndrome, which results in low levels of male hormones, sterility, breast enlargement, and small testes. If cancer does arise in the second testicle, it is nearly always a new disease rather than a metastasis from the first tumor.
In men under the age of 60, 95% of testicular tumors originate in the germ cells, the special sperm-forming cells within the testicles. There are two main types of testicular cancer, seminomas and nonseminomas (also called teratoma). Pure Seminomas account for about 40 percent of all testicular cancer and are made up of immature germ cells. Usually, seminomas are slow growing and tend to stay localized in the testicle for long periods. On the other hand, nonseminomas are a group of cancers that often occur in combination with one another, including choriocarcinoma, embryonal carcinoma, immature teratoma and yolk sac tumors. Nonseminomas arise from more mature, specialized germ cells and tend to be more aggressive than seminomas. Other forms of testicular cancer include Leydig and sertoli cell tumors. Rarer tumors such as PNET, leiomyosarcoma, rhabdomyosarcoma, mesothelioma and others can arise in the testicle.
The staging of testicular cancer is based on the revised criteria of TNM staging by the American Joint Committee for Cancer (AJCC) published in 1988. Staging is the process of describing the extent to which cancer has spread from the site of its origin. It is used to assess a patient's prognosis and to determine the choice of therapy. The stage of a cancer is determined by the size and location in the body of the primary tumor, and whether it has spread to other areas of the body. Staging involves using the letters T, N and M to assess tumors by the size of the primary tumor (T); the degree to which regional lymph nodes (N) are involved; and the absence or presence of distant metastases (M)—cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes. Each of these categories is further classified with a number 1 through 4 to give the total stage. Once the T, N and M are determined, a “stage” of I, II, III or IV is assigned. Stage I cancers are small, localized and usually curable. Stage II and III cancers typically are locally advanced and/or have spread to local lymph nodes. Stage IV cancers usually are metastatic (have spread to distant parts of the body) and generally are considered inoperable.
Testicular cancer is almost always curable if it is found early, even if it has spread to other parts of the body. Specifically, the survival rate for men diagnosed with Stage I seminoma is about 99%. The survival rate for men with Stage I non-seminoma is about 98%. Cure rates for Stage II tumors range above 90%, while cure rates for Stage III tumors vary between 50–80%. Moreover, there is a very low recurrent rate for both seminomas and nonseminomas (less than 5%) after a patient has been free of the disease.
Testicular cancer can be treated with surgery, radiation therapy, chemotherapy, surveillance, or a combination of these treatments. The most common surgical operation to treat testicular cancer is complete removal of the testicle (called an Inguinal Orchiectomy). The surgeon does not just remove part of the testicle because of the risk of spreading the disease. Sometimes it is also necessary to remove lymph nodes deep in the abdomen (called RPLND surgery) since testicular cancer usually spreads via a very predictable route through the lymph nodes upwards to the lungs, and then outward to the liver, brain, and elsewhere. Additionally, tumors that have spread to other parts of the body may be partly or entirely removed by surgery. Unfortunately, although surgery to remove the lymph nodes does not change a man's ability to have an erection or an orgasm, but the operation can cause infertility because it may interfere with the nerves involved in ejaculation.
Radiation therapy, like surgery, is a local treatment and affects only the cells in the treated area. Seminomas are highly sensitive to radiation while nonseminomas are much less sensitive to radiation. Further, radiation therapy may interfere with sperm production, although the effect is usually temporary. Some other unpleasant effects of radiation therapy include diarrhea and vomiting. There may also be skin reactions in the area being treated.
Several drugs are typically used to treat testicular cancer: Platinol (cisplatin), Vepesid or VP-16 (etoposide) and Blenoxane (bleomycin sulfate), Bleomycin, Etoposide, and Cisplatin. Additionally, Ifex (ifosamide), Velban (vinblastine sulfate) and others may be used. Many medical professionals regard Platinol as the “magic bullet” for treating testicular cancer. It is the primary reason that testicular cancer is considered to be a curable disease. However, chemotherapy causes many side effects because it damages not only cancer cells, but other rapidly growing cells as well, such as hair and gum tissue. Undesirable side effects include temporary hair loss, mouth sores, anemia (decreased numbers of red blood cells that may cause fatigue, dizziness, and shortness of breath), leukopenia (decreased numbers of white blood cells that may lower resistance to infection), thrombocytopenia (decreased numbers of platelets that may lead to easy bleeding or bruising), and gastrointestinal symptoms like nausea, vomiting, and diarrhea.
Oftentimes, chemotherapy with radiation in adjunct to surgery is used. In general, chemotherapy can achieve long-term survival rates of up to 15% to 20%, even in patients with recurrent or metastatic disease (Ali et al., 2000, Oncology 14(8):1223–30). Unfortunately, the high initial response rates to first line chemotherapy does not appear to translate into a survival benefit (Kohno and Kitahara, 2001, Gan To Kagaku Ryoho 28(4):448–53). Moreover, there are many undesirable side effects associated with chemotherapy such as temporary hair loss, mouth sores, anemia (decreased numbers of red blood cells that may cause fatigue, dizziness, and shortness of breath), leukopenia (decreased numbers of white blood cells that may lower resistance to infection), thrombocytopenia (decreased numbers of platelets that may lead to easy bleeding or bruising), and gastrointestinal symptoms like nausea, vomiting, and diarrhea.
The identification of active chemotherapeutic agents against cancers traditionally involved the use of various animal models of cancer. The mouse has been one of the most informative and productive experimental system for studying carcinogenesis (Sills et al., 2001, Toxicol Letters 120:187–198), cancer therapy (Malkinson, 2001, Lung Cancer 32(3):265–279; Hoffman R M., 1999, Invest New Drugs 17(4):343–359), and cancer chemoprevention (Yun, 1999, Annals NY Acad Sci. 889:157–192). Cancer research started with transplanted tumors in animals which provided reproducible and controllable materials for investigation. Pieces of primary animal tumors, cell suspensions made from these tumors, and immortal cell lines established from these tumor cells propagate when transplanted to animals of the same species.
To transplant human cancer to an animal and to prevent its destruction by rejection, the immune system of the animal are compromised. While originally accomplished by irradiation, thymectomy, and application of steroids to eliminate acquired immunity, nude mice that are athymic congenitally have been used as recipients of a variety of human tumors (Rygaard, 1983, in 13th International Cancer Congress Part C, Biology of Cancer (2), pp37–44, Alan R. Liss, Inc., NY; Fergusson and Smith, 1987, Thorax, 42:753–758). While the athymic nude mouse model provides useful models to study a large number of human tumors in vivo, it does not develop spontaneous metastases and are not suitable for all types of tumors. Next, the severe combined immunodeficient (SCID) mice is developed in which the acquired immune system is completely disabled by a genetic mutation. Human lung cancer was first used to demonstrate the successful engraftment of a human cancer in the SCID mouse model (Reddy S., 1987, Cancer Res. 47(9):2456–2460). Subsequently, the SCID mouse model have been shown to allow disseminated metastatic growths for a number of human tumors, particularly hematologic disorders and malignant melanoma (Mueller and Reisfeld, 1991, Cancer Metastasis Rev. 10(3):193–200; Bankert et al., 2001, Trends Immunol. 22:386–393). With the recent advent of transgenic technology, the mouse genome has become the primary mammalian genetic model for the study of cancer (Resor et al., 2001, Human Molec Genet. 10:669–675).
While surgery, chemotherapeutic agents, hormone therapy, and radiation are useful in the treatment of testicular cancer, there is a continued need to find better treatment modalities and approaches to manage the disease that are more effective and less toxic, especially when clinical oncologists are giving increased attention to the quality of life of cancer patients. The present invention provides an alternative approach to cancer therapy and management of the disease by using an oral composition comprising yeasts.
2.2 Yeast-Based Compositions
Yeasts and components thereof have been developed to be used as dietary supplement or pharmaceuticals. However, none of the prior methods uses yeast cells which have been cultured in an electromagnetic field to produce a product that has an anti-cancer effect. The following are some examples of prior uses of yeast cells and components thereof:
U.S. Pat. No. 6,197,295 discloses a selenium-enriched dried yeast product which can be used as dietary supplement. The yeast strain Saccharomyces boulardii sequela PY 31 (ATCC 74366) is cultured in the presence of selenium salts and contains 300 to about 6,000 ppm intracellular selenium. Methods for reducing tumor cell growth by administration of the selenium yeast product in combination with chemotherapeutic agents is also disclosed.
U.S. Pat. No. 6,143,731 discloses a dietary additive containing whole β-glucans derived from yeast, which when administered to animals and humans, provide a source of fiber in the diet, a fecal bulking agent, a source of short chain fatty acids, reduce cholesterol and LDL, and raises HDL levels.
U.S. Pat. No. 5,504,079 discloses a method of stimulating an immune response in a subject utilizing modified yeast glucans which have enhanced immunobiologic activity. The modified glucans are prepared from the cell wall of Saccharomyces yeasts, and can be administered in a variety of routes including, for example, the oral, intravenous, subcutaneous, topical, and intranasal route.
U.S. Pat. No. 4,348,483 discloses a process for preparing a chromium yeast product which has a high intracellular chromium content. The process comprises allowing the yeast cells to absorb chromium under a controlled acidic pH and, thereafter inducing the yeast cells to grow by adding nutrients. The yeast cells are dried and used as a dietary supplement.
Citation of documents herein is not intended as an admission that any of the documents cited herein is pertinent prior art, or an admission that the cited documents are considered material to the patentability of the claims of the present application. All statements as to the date or representations as to the contents of these documents are based on the information available to the applicant and does not constitute any admission as to the correctness of the dates or contents of these documents.